Osteoarthritis (OA) is a leading cause of pain and functional limitation in the United States. There are significant individual and ethnic group differences in the experience of OA. An improved understanding of factors contributing to the disparities and a biomarker reflecting the variability is needed. The research goals and career development training objectives identified in this K23 Mentored Patient-Oriented Research Career Development Award application have been developed to obtain the training and experience to pursue investigations of the biological interface of chronic pain and psychosocial stress in knee OA. Entitled Biological Markers of System Burden in Symptomatic Knee OA: A Prospective Study, the proposed study expands on current research supported in part through the Basic Behavioral and Social Science Opportunity Network (OppNet) specific to Dr. Sibille's research interests and career ambitions. Additionally, the proposed research aligns with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Long Range Plan for Fiscal Years 2010-2014 and the 2010 NIAMS Roundtable Summary. My career goals are to: 1) excel in an academic medical setting as a clinical/translational pain investigator with expertise in osteoarthritis involved in patient-oriented research and 2) contribute to the research and medical community through scholarship and education with an overall goal of improving the management, functioning, and quality of life for individuals with osteoarthritis and other pain-related conditions. My career development training objectives incorporate activities and experiences pertinent to my research goals and necessary to obtain R01 funding by 2016. Objective 1: Develop a comprehensive knowledge-base in osteoarthritis Objective 2: Broaden skills in multi-modal assessment of pain and functional limitations Objective 3: Increase understanding of genetics and stress-related biological systems Objective 4: Enhance management skills necessary to function as an independent researcher Objective 5: Strengthen skills in clinical/translational research, statistics, and scholarship My career development research and training efforts will be guided by an exceptional mentoring team, Roger Fillingim, Ph.D., Primary Mentor, will provide guidance and oversight in the multi-modal assessment of pain and functional limitations; the integration of biological and psychosocial factors; and my overall career development. Roland Staud, M.D., will oversee the development of a comprehensive knowledge-base in osteoarthritis. Christiaan Leeuwenburgh, Ph.D., Co-Mentor, will provide direction in areas related to metabolic processes, evaluating biological markers, and developing the skills necessary for translational investigation. Taimour Langaee, Ph.D., Co-Mentor, will assist with training and development in the areas of immunology, genetics, and telomere measures. Bruce McEwen, Ph.D., Consultant/Co-Mentor, will direct my training specific to neuroendocrine functioning, the effects of stress on health, and the application of the allostatic load model in the study of knee osteoarthritis. My transition to research independence will also be benefited by relationships developed in the OA Network, an advisory and collaborative group of clinician/researchers. A comprehensive training plan has been developed that includes didactic coursework, clinical and laboratory experience, directed study; individual and group mentoring meetings; involvement in lab meetings, research interest groups, journal clubs; attendance and presentations at professional conferences; manuscript and grant development; research responsibilities; and academic/department contributions. Completion of the proposed training plan will include obtaining a Certificate of Clinical Translational Research by 2014 through the University of Florida Clinical and Translational Science Institute (CTSI). The training environment at the University of Florida is outstanding. In addition to the educational programs and resources available through the CTSI, I have the opportunity to train and work with accomplished basic and clinical researchers through the Comprehensive Center for Pain Research, the College of Dentistry, the Pain Research and Intervention Center of Excellence, and the Claude D. Pepper Older Americans Independence Center. The proposed research study is novel, multidisciplinary, and translational. The objectives of the study are to prospectively evaluate associations of pain and functional limitations with a developing measure of system burden in ethnically diverse older adults with and without knee OA and explore the role of various biopsychosocial factors that may be protective or increase vulnerability for pain and functional decline. There are numerous opportunities with significant clinical implications to extend the translational research efforts proposed. Long-term goals are to elucidate biological markers of system burden in knee OA, delineate resilience and vulnerability factors for prevention and treatment, and establish a composite of biomarkers for evaluating the efficacy of clinical interventions. Importantly, the information generated by this research will make a significant scientific contribution as this represents the first study to prospectively examine biological markers of system burden, knee OA status, pain severity, and functional limitations among ethnically diverse older adults with and without knee OA.